IL-10 Elicits IFNγ-Dependent Tumor Immune Surveillance
| Autor: | Gulesi Ayanoglu, Erin Murphy, Scott P. Turner, Amy M Beebe, Ivan H. Chan, John B. Mumm, Venkataraman Sriram, Xueqing Zhang, Catherine Sheppard, Jeff Grein, Beth Basham, Martin Oft, Satya Medicherla, Jan Emmerich, Melanie A. Kleinschek, Lingling Wu, Michael Judo, Steven J. Blaisdell, Terrill K. McClanahan, Susan Cannon-Carlson, John L. Langowski, Danling Gu, Kyu Hong, Wolfgang Seghezzi, Smita Mauze, Brittany C. Paporello, Bela Desai, Saraswathi Naravula, Jie Dai, Drake LaFace, Collette M. Cutler |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cytotoxicity
Immunologic Cancer Research Skin Neoplasms Antigen presentation Interleukin-10 Receptor alpha Subunit Transplantation Heterologous Antineoplastic Agents Breast Neoplasms Mice Transgenic Biology CD8-Positive T-Lymphocytes Granzymes Interferon-gamma Mice Immune system Interferon Cell Line Tumor medicine Cytotoxic T cell Animals Humans Mice Inbred BALB C Perforin Mammary Neoplasms Experimental Neoplasms Experimental Cell Biology Interleukin-10 Tumor Burden Transplantation Mice Inbred C57BL Interleukin 10 Tumor Escape Granzyme Oncology Immunology biology.protein Female Neoplasm Transplantation Spleen medicine.drug |
| Zdroj: | Cancer Cell. 20(6):781-796 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccr.2011.11.003 |
| Popis: | Summary Tumor immune surveillance and cancer immunotherapies are thought to depend on the intratumoral infiltration of activated CD8 + T cells. Intratumoral CD8 + T cells are rare and lack activity. IL-10 is thought to contribute to the underlying immune suppressive microenvironment. Defying those expectations we demonstrate that IL-10 induces several essential mechanisms for effective antitumor immune surveillance: infiltration and activation of intratumoral tumor-specific cytotoxic CD8 + T cells, expression of the Th1 cytokine interferon-γ (IFNγ) and granzymes in CD8 + T cells, and intratumoral antigen presentation molecules. Consequently, tumor immune surveillance is weakened in mice deficient for IL-10 whereas transgenic overexpression of IL-10 protects mice from carcinogenesis. Treatment with pegylated IL-10 restores tumor-specific intratumoral CD8 + T cell function and controls tumor growth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|